We are investigating the deviation from the triple-helical polyproline-II conformation of a proline-poor sequence within collagen. This segment, GTPGPQGIAGQRGVV, hereafter referred to as P15, acts as a cell adhesion peptide: It binds to receptors on cells and promotes differentiation of these cells. Small peptides derived from P15 act in a similar fashion. There are numerous practical applications of research relating to these peptides, since the ability to induce cell binding and differentiation is relevant to wound healing, tissue repair, and the design of medical and dental prostheses. Our ultimate goal is to design, for biomedical applications, a non-peptide compound that mimics the structure and biological activity of the active core of P15 and the P15-derived peptides; this core appears to be the sequence Isoleucine-Alanine. The recent focus of this project has been the examination of ways in which a beta-bend could fit into a native collagen molecule. In particular, we have examined how a bend at the central GIAG could be surrounded by beta-strands formed by the two other segments of P15, GTPGPQ and QGRVV. The beta-strand conformation is more extended than the polyproline-II conformation found in the majority of the residues of native collagen, and would allow P15 to form a bend at its center while still allowing a smooth connection to polyproline-II segments at the termini of P15. We are examining, using graphical modelling, and molecular mechanics and molecular dynamics calculations, ways in which the beta-bend and the two beta-strand modules can be linked to each other and to the rest of the collagen molecule in a geometrically and energetically reasonable manner. MidasPlus and the facilities of the UCSF Computer Graphics Laboratory have been and will be used for graphical modelling and visualization of the molecular geometry, for preparing the peptides and collagen sequences in starting structures for the theoretical calculations, and for monitoring the structures as they undergo these calculations.